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Phase II, single-arm, open-label single center study that assess clinical feasibility and safety of 3 cycles neoadjuvant Sintilimab plus chemotherapy in EGFR-mutant stage IIB-IIIB NSCLC (excluding N3) followed by optional adjuvant treatment upon investigators' decisions.
35 eligible patients will be enrolled and 3 cycles of Sintilimab 200mg + doublet platinum-based chemotherapy will be administered. Dynamic blood samples before, during or after neoadjuvant treatment will be obtained for exploratory analysis. Patients who showed inferior response to neoadjuvant treatment leading to unresectable disease will be scheduled for local radiation or other potential subsequent treatment regarding multidisciplinary discussion. After completion of local treatment (surgery or radiation), patients will be provided with optional adjuvant treatment including EGFR-TKI upon investigators' consideration. Patients will be followed with 5 years after surgery. The primary objective of the study is major pathological response (MPR) defined as no more than 10% residual tumor found in primary lung cancer.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sintilimab plus chemo | Experimental | 3 cycles of neoadjuvant Sintilimab (200mg every 3 weeks) with nab-paclitaxel and carboplatin (nab-paclitaxel 260 mg/m2, d1 and carboplatin AUC 5, d1 every 3 weeks) will be administered before surgery, followed by optional adjuvant treatment including EGFR-TKIs for up to 1 year or till disease progression or unacceptable toxicity. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sintilimab | Biological | 200mg Q3W |
| |
| Carboplatin |
| Measure | Description | Time Frame |
|---|---|---|
| Major Pathological Response (MPR) | Percentage of Participants with Major Pathologic Response. MPR was defined as percentage of tumor cells within tumor bed less than 10% for primary lung lesions. | MPR will be assessed within 2 weeks after surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) | ORR is the number of participants with a Complete Response (CR) and Partial Response (PR) divided by the total number of randomized participants per arm, then multiplied by 100. Response is based on the Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria. Complete Response (CR) was defined as the disappearance of all target lesions. Partial Response (PR) was defined as at least a 30% decrease in sum of longest diameter of target lesions compared to baseline or the complete disappearance of target lesions, with persistence of 1 or more nontarget lesion(s) and no new lesions. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Wen-zhao Zhong, PhD | Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences | Guangzhou | Guangdong | 510080 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32386568 | Background | Shu CA, Gainor JF, Awad MM, Chiuzan C, Grigg CM, Pabani A, Garofano RF, Stoopler MB, Cheng SK, White A, Lanuti M, D'Ovidio F, Bacchetta M, Sonett JR, Saqi A, Rizvi NA. Neoadjuvant atezolizumab and chemotherapy in patients with resectable non-small-cell lung cancer: an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2020 Jun;21(6):786-795. doi: 10.1016/S1470-2045(20)30140-6. Epub 2020 May 7. | |
| 32979984 |
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After the primary data including translational analysis has been published, IPD of detailed clinical information and comics data could be available from principle investigator upon reasonable request.
After the primary data including translational analysis has been published, IPD of detailed clinical information and comics data could be available. Approximate 48 months after initiation of enrollment.
IPD could be accessed from principle investigator upon reasonable request.
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| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
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| ID | Term |
|---|---|
| C000632826 | sintilimab |
| D016190 | Carboplatin |
| D013660 | Taxes |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D004467 | Economics |
| D004472 | Health Care Economics and Organizations |
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A Simon two-stage design was applied. Primary endpoint for this study was MPR. The unacceptable response rate for MPR was less than 10% and desirable response rate was 30%. The error rate for alpha was set as 0.05 and 0.1 for beta. The Optimal assay was chosen and at least 35 patients should be enrolled to meet adequate statical power. 18 patients would be enrolled in stage I and at least 2 patient achieved MPR were required to proceed stage II enrollment. Overall, if 6 achieved MPR out of 35 patients, the study would be determined as positive.
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| Drug |
AUC 5, d1 every 3 weeks |
|
| Nab paclitaxel | Drug | 260 mg/m2, d1 every 3 weeks |
|
| Tumor response will be evaluated within 3-4 weeks after last dose of neoadjuvant treatment |
| Pathological Complete Response (pCR) | Evaluation of the pathological complete response: The pathological complete response is defined as the absence of residual tumor in both lung and lymph nodes after neoadjuvant treatment. | pCR will be assessed within 2 weeks after surgery |
| Progression-free Survival (PFS) | The period after initiation of neoadjuvant treatment when no disease progression can be detected. | From date of initiation of neoadjuvant treatment till the date of first documented disease progression or death, whichever came first, assessed up to 36 months. |
| Overall Survival (OS) | The period after initiation of neoadjuvant treatment when no all-cause death can be detected. | From date of initiation of neoadjuvant treatment till the date of all-cause death, assessed up to 60 months. |
| Adverse Events (AEs) | Incidence of all grade AE which has been confirmed to be correlated with neoadjuvant treatment | From date of initiation of neoadjuvant treatment till treatment discontinuation, assessed up to 14 weeks. |
| Background |
| Provencio M, Nadal E, Insa A, Garcia-Campelo MR, Casal-Rubio J, Domine M, Majem M, Rodriguez-Abreu D, Martinez-Marti A, De Castro Carpeno J, Cobo M, Lopez Vivanco G, Del Barco E, Bernabe Caro R, Vinolas N, Barneto Aranda I, Viteri S, Pereira E, Royuela A, Casarrubios M, Salas Anton C, Parra ER, Wistuba I, Calvo V, Laza-Briviesca R, Romero A, Massuti B, Cruz-Bermudez A. Neoadjuvant chemotherapy and nivolumab in resectable non-small-cell lung cancer (NADIM): an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2020 Nov;21(11):1413-1422. doi: 10.1016/S1470-2045(20)30453-8. Epub 2020 Sep 24. |
| 29658848 | Background | Forde PM, Chaft JE, Smith KN, Anagnostou V, Cottrell TR, Hellmann MD, Zahurak M, Yang SC, Jones DR, Broderick S, Battafarano RJ, Velez MJ, Rekhtman N, Olah Z, Naidoo J, Marrone KA, Verde F, Guo H, Zhang J, Caushi JX, Chan HY, Sidhom JW, Scharpf RB, White J, Gabrielson E, Wang H, Rosner GL, Rusch V, Wolchok JD, Merghoub T, Taube JM, Velculescu VE, Topalian SL, Brahmer JR, Pardoll DM. Neoadjuvant PD-1 Blockade in Resectable Lung Cancer. N Engl J Med. 2018 May 24;378(21):1976-1986. doi: 10.1056/NEJMoa1716078. Epub 2018 Apr 16. |
| 30922878 | Background | Reck M, Mok TSK, Nishio M, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, Rodriguez-Abreu D, Moro-Sibilot D, Thomas CA, Barlesi F, Finley G, Lee A, Coleman S, Deng Y, Kowanetz M, Shankar G, Lin W, Socinski MA; IMpower150 Study Group. Atezolizumab plus bevacizumab and chemotherapy in non-small-cell lung cancer (IMpower150): key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised, open-label phase 3 trial. Lancet Respir Med. 2019 May;7(5):387-401. doi: 10.1016/S2213-2600(19)30084-0. Epub 2019 Mar 25. |
| 36123526 | Background | Zhang C, Chen HF, Yan S, Wu L, Yan LX, Yan XL, Yue DS, Xu CW, Zheng M, Li JS, Liu SY, Yang LL, Jiang BY, Ou QX, Qiu ZB, Shao Y, Wu YL, Zhong WZ. Induction immune-checkpoint inhibitors for resectable oncogene-mutant NSCLC: A multicenter pooled analysis. NPJ Precis Oncol. 2022 Sep 19;6(1):66. doi: 10.1038/s41698-022-00301-8. |
| 42256683 | Derived | Zhang C, Jiang BY, Yan LX, Peng LS, Li JH, Chen ZY, Sun YX, Su J, Liao RQ, Dong S, Yan HH, Xu CR, Zhou Q, Yang XN, Hu Z, Wu YL, Zhong WZ. Neoadjuvant sintilimab plus chemotherapy in EGFR-mutant non-small cell lung cancer (NEOTIDE/CTONG2104): phase II trial and correlative genomic analysis in China. EClinicalMedicine. 2026 May 28;96:103994. doi: 10.1016/j.eclinm.2026.103994. eCollection 2026 Jun. |
| D013899 |
| Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |